AB0921 EFFICACY AND SAFETY OF MACITENTAN IN REFRACTORY DIGITAL ULCERS
Authors: M. Retuerto-Guerrero, C. Moriano, I. Castellví, B. Atienza-Mateo, E. Diez Álvarez
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Raynaud's phenomenon (Rp) is used to describe a symptom complex caused by digital vascular involvement. The presence of digital ulcerations (DU) should prompt further evaluation for secondary causes of Rp. Among the conditions that may be associated with Rp are Systemic Autoimmune Rheumatic Diseases (SARDs), especially Systemic Sclerosis (SSc). DU are a major cause of morbidity and have a high recurrence rate in most patients and may be refractory to multiple treatments. Macitentan is a dual endothelin receptor antagonist authorized to treat pulmonary hypertension. Its efficacy in the treatment of DU associated to SSc has been assessed in two clinical trials (DUAL-1 and DUAL-2)<sub>1</sub>, without any visible effects on their prevention or reduction. However, these trials have been criticized on the methodology and profile of the patients included. <h3>Objectives</h3> To assess efficacy and safety of Macitentan in patients suffering from SARDs and refractory DU. <h3>Methods</h3> Spanish observational multicentric study. Data were retrospectively obtained from medical records of 10 patients suffering from SARDs and refractory DU secondary to severe Rp treated with Macitentan 10mg/daily. Total response was defined as the complete healing of DU and partial improvement as the reduction of the number or size of ulcers. Patients with ischemic ulcers caused by other factors were excluded. <h3>Results</h3> We identified 10 patients who has received treatment with Macitentan for DU, median age 59 years (IQR 51-68), 80% female, with a median Rp and DU duration of 56 (IQR 14-214) and 25 (IQR 9-215) months (Table 1). Eight patients were diagnosed with limited SSc; anti-nuclear abs, anti-centromere abs and anti-phospholipidic abs were positive in 90%, 80% and 20% of the patients. Most patients (90%) had received previously treatment with Bosentan, and the reason for withdrawal was inefficacy in 4 cases (44%) and adverse effects (liver toxicity) in 5 (56%). 8 patients had received Intravenous prostanoids with no response. In the beginning of Macitentan the number of DU was 5.5 (IQR 2.3-6) and digital gangrene was reported in one case. Two patients were treated with Macitentan in monotherapy, 6 in combination with calcium antagonists and 2 received triple therapy (Macitentan + Calcium antagonists + PDE5 inhibitor). Just one patient stopped the treatment for adverse effects (lower limb edema). Median follow-up of patients who didn't discontinue the treatment was 3.9 (IQR 2.4-5.7) years. 78% (7/9) of patients had a sustained complete response and 22% (2/9) had a partial response. <h3>Conclusion</h3> Our data show that Macitentan is an effective agent for ischemic digital refractory ulcers in patients suffering from SARDs with a favorable safety profile in clinical practice. <h3>Reference</h3> [1]Khanna D, Denton CP, Merkel PA, Krieg T, Le Brun FO, Marr A, Papadakis K, Pope J, Matucci-Cerinic M, Furst DE; DUAL-1 Investigators; DUAL-2 Investigators. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA. 2016 May 10;315(18):1975-88. doi: 10.1001/jama.2016.5258. PMID: 27163986. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.